There is increasing evidence for the presence of type-C viral genetic information in all mammalian cells. Some of the genetic loci involved in regulating expression of such viral information have been well characterized. There is, however, a lack of understanding of the molecular mechanisms involved. The primary thrust of this proposal will address itself to understanding the mechanism of action of H-2 linked genes in conferring resistance or susceptibility to virus-induced leukemia. Two model systems will be investigated (1) H-2 linked control of Radiation Leukemia virus (Rad LV) induced neoplasia, and (2) regulation of cell and humoral-mediated immunity to AKR tumor cells by H-2 linked genes. Present understanding of the role of H-2 linked genes in conferring resistance to murine leukemia viruses is in a primitive state. The currently proposed studies will broaden our knoledge of genetic mechanisms by examining immunological as well as nonimmunological aspects. The specific immunological studies proposed will examine the type of cells mobilized during the immune response; the determinants present on such cells that mark them as a subclass of lymphocytes; the type of humoral and cell-mediated responses elicited (e.g., cytotoxic antibody, neutralizing antibody, etc.); the antigenic determinants eliciting such a response; and the association of these determinants with detectable H-2 gene products. Additional studies will examine the notion that susceptibility to viral leukemia results from loss of H-2 and/or virus associated antigens from virus infected and/or transformed cells, enabling such cells to escape immunological destruction, and H-2 effects on virus assembly.